Statin safety: Lessons from new drug applications for marketed statins
Statin safety: Lessons from new drug applications for marketed statins
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DOI：
10.1016/j.amjcard.2005.12.009
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发表时间：
2006-04-17
影响因子：
2.8
通讯作者：
Jacobson, TA
中科院分区：
文献类型：
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作者：
Jacobson, TA
安全性已成为他汀类药物治疗血脂异常的中心问题。对所有3-羟基-3-甲基戊二酰辅酶A(HMG-CoA)还原酶抑制剂或他汀类药物的新药申请(NDA)和美国食品和药物管理局(FDA)网站进行了审查，重点是西立伐他汀和瑞舒伐他汀。这些发现为这类药物的不良事件发生率提供了洞察力，并支持了他汀类药物相对于相关风险的显著好处。这些数据描述了他汀类药物相关的肝、肌肉和肾脏不良事件的性质。尽管转氨酶水平随着他汀类药物剂量的增加而升高，但他汀类药物的NDA数据并不支持他汀类药物治疗和肝毒性之间的明确相关性。他汀类药物引起的肌病是一种相对罕见的事件(千分之一)，横纹肌溶解更罕见(万分之一)。西立伐他汀NDA和它的补充NDA第一次证明了他汀类药物与肌病之间存在明确的剂量-反应关系，并且存在阈值效应，超过这个阈值后，肌肉毒性会显著增加。根据瑞舒伐他汀NDA的数据，蛋白尿被确认为他汀类药物治疗的结果，随后的分析表明，一种与剂量相关但短暂的类别效应。在细胞培养中的研究表明，其机制是对近端肾小管的药物作用。现有证据表明，目前批准的他汀类药物没有明显的肾脏毒性，因为肾功能或肾小球没有下降。随着时间的推移，滤过率已被记录在案。总体而言，目前上市的他汀类药物在肝脏、肌肉和肾脏问题上具有非常有利的益处-风险关系。(C)2006 Elsevier Inc.保留所有权利。
Safety has become a central issue in the management of dyslipidemia with statins. A review of New Drug Applications (NDAs) and the US Food and Drug Administration (FDA) Web site was conducted for all 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or statins, with a major focus on cerivastatin and rosuvastatin. The findings provide insight into the incidence of adverse events for this class of drugs and support the significant benefits of statins relative to associated risks. These data delineate the nature of statin associated liver, muscle, and renal adverse events. Although transaminase levels increase in a dose-related fashion with statins, a definitive correlation between statin therapy and hepatotoxicity is not supported by statin NDA data. Statin-induced myopathy is a relatively rare event (1 in 1,000) and rhabdomyolysis is even rarer (1 in 10,000). The cerivastatin NDA, along with its supplementary NDA, was the first to demonstrate a clear statin dose-response relation with myopathy and a threshold effect above which myotoxicity increases significantly. Proteinuria was identified as a consequence of statin therapy with data from the rosuvastatin NDA, and subsequent analysis suggests a class effect that is dose related but transient. Studies in cell culture suggest the mechanism is a pharmacologic effect on the proximal renal tubule. The available evidence suggests no clear renal toxicity with currently approved statins, because no declines in renal function or glomerular. filtration rate have been documented over time. Overall, currently marketed statins have a very favorable benefit-to-risk relation with respect to liver, muscle, and renal issues. (c) 2006 Elsevier Inc. All rights reserved.